Human cytomegalovirus (HCMV) is ubiquitously distributed in the human population. In immunocompetent adults infections are mainly asymptomatic, but in immunocompromised patients, such as transplant recipients or AIDS patients, life threatening infections occur at a high rate. HCMV is also the leading cause of birth defects among congenitally transmitted viral infections.
Various substituted heterocyclic compounds are inhibitors of the HCMV terminase enzyme. Included in these heterocycles are quinazolines related to Compound A, as defined and described below. These compounds and pharmaceutically acceptable salts thereof are useful in the treatment or prophylaxis of infection by HCMV and in the treatment, prophylaxis, or delay in the onset or progression of HCMV infection. Representative quinazoline compounds that are useful for treating HCMV infection are described, for example, in U.S. Pat. No. 7,196,086. Among the compounds disclosed in U.S. Pat. No. 7,196,086, is (S)-2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetic acid, hereinafter referred to as Compound A. Compound A is a known inhibitor of HCMV terminase. The structure of Compound A is as follows:

U.S. Pat. Nos. 7,196,086 and 8,084,604 and PCT Publication No. WO2015/088931 disclose methodology and synthetic routes that can be used to prepare Compound A and related quinazoline-based HCMV terminase inhibitors. However, the currently known methods have various drawbacks and there remains a need for improved synthetic methods for preparing Compound A and related compounds.